Model Systems Core Project Summary Animal models are revolutionizing our understanding of IDDs, and such models provide fundamental insights into biological pathways and often display phenotypes that are similar to clinical indicators of the human disease, providing an opportunity to deduce mechanisms of disease pathology, and also to develop therapies. The Model Systems Core (MSC) is organized into three units ? the Animal Behavior Unit, the Neuropathology Unit, and the Functional Assessments Unit. The goal of the MSC is to provide expertise, resources, and assessment to Center investigators involved in the creation and evaluation of animal and cellular models relevant to IDD, drawing on strengths in genetics, brain imaging, bioinformatics, and neuroscience to provide advice, assistance, and services to investigators at all career stages. The specific aims are: 1) Provide consultation to investigators needing assessments in animal behavior, pathology and CNS function. A priority for the Core Directors and Unit leaders is to make certain that first-time users are guided to appropriate services and understand the complement of available resources; 2) Characterize neurological deficits in rodent and cellular models of IDD submitted by investigators. The MSC is configured to provide access to a range of experimental approaches including: i) functional phenotyping of mice and rats (learning and memory, motor/sensorimotor functions, alterations in emotionality/motivation, social interactions, sensory behavioral functions, depression-like behaviors, and behaviors related to models of Autism Spectrum Disorder; ii) histological services to evaluate IDD-related changes at the cellular level; and, iii) sophisticated, non- invasive imaging (MRI, functional connectivity optical imaging) as well as in vitro (including advanced microscopy of cellular models) and in vivo neurophysiological assessments, such as electroencephalography (EEG), polysomnography, and somatosensory evoked potentials in animal models of IDD; 3) Assess novel therapies and/or biomarkers in models of IDD in animal behavior, pathology and CNS function. Each Unit within the MSC is already configured to allow rapid, sensitive testing of novel therapies and/or biomarkers for IDD models; 4) Integrate information across units, cores and other existing facilities within the University. Together with the Unit leaders, MSC Directors will provide guidance for institutional resources both within and outside of the MSC. Together with the Scientific Advisory Panel, MSC Directors will also help investigators identify the best model system for a specific gene locus, clinical phenotype and/or screening for compounds to reverse disrupted function. WUSTL has state-of-the-art expertise and facilities for zebrafish, C. elegans, and/or Drosophila models of human disease.